Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

The synapse is a shotgun

15.07.2005


New model challenges textbook definition



Researchers have constructed a new detailed map of the three-dimensional terrain of a synapse -- the junction between neurons which are critical for communication in the brain and nervous system. The "nano-map," which shows the tiny spines and valleys resolved at nanometer scale, or one-billionth of a meter, has already proven its worth in changing scientists’ views of the synaptic landscape.

Using the map as a guide, the research team, led by Howard Hughes Medical Institute investigator Terrence Sejnowski, has developed a biologically accurate computer simulation of synaptic function. The simulation combines 3-D electron microscope maps with computer simulation and physiological measurements from real neurons. Their in silico modeling indicates that the synapse may behave more like a shotgun than a rifle when it comes to firing the neurotransmitters involved in neuronal communication.


The textbook view of the synapse describes it as a place where rifle-like volleys of neurotransmitter are launched from one defined region of the sending neuron to another defined target on the receiving neuron. In contrast, the new data suggest that synapse can act like a shotgun, firing buckshot-like bursts of neurotransmitter to reach receptors arrayed beyond the known receiving sites. The researchers say that right now they have little idea of how the synaptic shotgun functions.

The research was published in the July 15, 2005, issue of the journal Science. Sejnowski, who is at The Salk Institute, and colleagues Darwin Berg and Mark Ellisman, both of the University of California, San Diego, led the research team, which also included co-authors from Carnegie Mellon University and the University of Pittsburgh.

In the collaborative studies, Ellisman and his colleagues first used electron microscopic tomography -- the microscopist’s equivalent of a CAT scan -- to create a detailed 3-D map of the synapse of a chick ciliary ganglion. This ganglion is a cluster of neurons that connect the brain to the iris of the eye. It launches the neurotransmitter acetylcholine from sac-like vesicles across the synapse to two types of receptors, called alpha 7 and alpha 3.

Sejnowski and his colleagues transformed their map into a functional computer model by incorporating the physiological details of neurotransmitter release sites and receptors. The researchers then compared the behavior of the model under different scenarios with the electrophysiological behavior of actual ganglia measured in Berg’s laboratory.

The results, said Sejnowski, provide evidence for a different concept of the synapse. "The image of this ganglion is not one of a simple synapse with a single release site, but multiple release sites. And it shows alpha 3 receptors within the postsynaptic region, but alpha 7 receptors outside this region. Our model showed that if we assumed that neurotransmitter is released only from vesicles in active zones, where everybody thinks it is released, we get a very bad match to actual properties of the neuron. But if we model broader neurotransmitter release, where these alpha 7 receptors are located, we can match the actual properties of the synapse very accurately." This type of broader neurotransmitter distribution is called ectopic release.

"We can only be sure of data on this one type of neuron, the ciliary ganglion," said Sejnowski. "But we are confident that this evidence points to ectopic release, and this means that you can’t really trust the traditional textbook view -- in which all the vesicles are released at the active zone -- that’s taken for granted now."

The function of shotgun neurotransmitter release is unknown, said Sejnowski. "There’s just nothing solid on our radar screen right now," he said. "There is speculation that ectopic release represents some sort of spillover that neurons use under certain circumstances. Or, it may be an alternative mode of neurotransmission that neurons use at different points in their life cycle." Sejnowski and his colleagues have initiated further studies using their simulation technique to confirm the ectopic release mechanism and explore its possible functions.

"Although we are convinced that ectopic release exists, any time you question an accepted concept, there will be doubt and resistance," said Sejnowski. "So, we will continue to develop this new picture of the synapse to convince doubters, because this is such a different way of looking at how the synapse functions." Sejnowski said that he and his collaborators will extend their study to other types of synapses that are more complex and difficult to study.

More broadly, said Sejnowski, the new 3-D modeling technique could offer a powerful tool for understanding neurological disease, such as myasthenia gravis, a common disorder in which a defect in nerve impulse transmission results in muscle weakness. In this and other neurological diseases, "there may be an anomaly at the receptor level, but it is impossible to pinpoint the problem with existing techniques. With our modeling technique, we can explore the detailed geometry of the damaged tissue and ask how much of that anomaly is caused by the geometry itself," he said.

"Once we have pinned down where the real problem is, we can use the model as a fantastic tool for drug discovery. We can tell drug developers precisely where the anomaly is and where they should focus drug discovery efforts."

Jim Keeley | EurekAlert!
Further information:
http://www.hhmi.org

More articles from Health and Medicine:

nachricht Millions through license revenues
27.04.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht New High-Performance Center Translational Medical Engineering
26.04.2017 | Fraunhofer ITEM

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Fighting drug resistant tuberculosis – InfectoGnostics meets MYCO-NET² partners in Peru

28.04.2017 | Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

 
Latest News

Wireless power can drive tiny electronic devices in the GI tract

28.04.2017 | Medical Engineering

Ice cave in Transylvania yields window into region's past

28.04.2017 | Earth Sciences

Nose2Brain – Better Therapy for Multiple Sclerosis

28.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>